Newborn Screening for Cystic Fibrosis

Abstract

The articles prior to January 2008 are part of the back file collection and are not available with a current paid subscription. To access the article, you may purchase it or purchase the complete back file collection here Richard B Parad, MD, MPH; Anne Marie Comeau, PhD For many years, newborn screening has been a successful public health measure for the pre-symptomatic detection of several disorders that are devastating to newborn infants. As discussed in other articles in this issue, early detection of disorders such as phenylketonuria (PKU) and congenital hypothyroidism (CH) allows for timely intervention that can preclude poor neurologic outcomes. While all states include tests for these disorders in their newborn screening programs, testing for other disorders vary by state. Recently, the purpose of newborn screening has broadened to include types of disorders in which overall outcome and survival may be improved with early therapy. One example is cystic fibrosis (CF), for which early nutritional therapy prevents malnutrition and improves growth. Newborn screening for genetic disorders has depended on biochemical and protein assays. With the explosion in DNA-based information resulting from the Human Genome Project and improving, rapid, inexpensive DNA diagnostic technologies, it seems likely that DNA testing in newborn screening will become increasingly important. Some disorders may only be detected using DNA diagnostics because other tests are not available or have poor sensitivity. CF provides a model for such testing and illustrates some challenges of population screening with a DNA test. CF differs somewhat from other disorders in conventional newborn screening panels for two reasons. It is the first newbom screening mat incorporates DNA testing into part of the primary testing algorithm. Also, a missed diagnosis will not result in a devastating neurologic problem, imminent pain, or death. However, the initiation of early preventive therapies may hold value through diminishing the severity of the disease, improving quality of Ufe, and prolonging outcome. Debate lingers over interpretation and value of follow-up results of non-randomized long-standing European and Australian screening programs that suggest CF newborn screening either improves or has equivocal impact on pulmonary outcome. Reviewed here is the experience that has led to current CF newborn screening practices. CYSTIC FIBROSIS CF is the most common lethal genetic autosomal recessive disorder. The disease affects approximately one in 3,000 Caucasians, one in 5,000 to 10,000 Hispanics, one in 17,000 African- Americans, and one in 30,000 Asian- Americans at birth. CF affects approximately 30,000 people in the United States. Half of CF patients die by age 32. About one in 29 Americans - more than 10 million people - is an unknowing, asymptomatic carrier of one defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. A child must inherit two defective copies of this gene, one from each parent, to develop CF. Severity of lung disease is the determining factor in quality and length of life. CF mainly affects the digestive system, respiratory tract, and male reproductive system. Because of damage to the pancreas, critical enzymes required for the digestion of fats are lacking. Many children present with severe malnutrition or failure to thrive. This problem can now be treated with supplemental pancreatic enzymes and fat-soluble vitamins. Lung infections begin early in these patients and are ultimately the cause of death. Recurrent bacterial pneumonia with irreversible lung damage and eventual respiratory failure is the hallmark of this disease. Nutritional support and antibiotic therapy have dramatically increased the survival rate for children with CF. However, despite longer survival, morbidity in this population remains considerable. As patients enter their adult years, they become increasingly debilitated, are unable to work, and suffer gradually deteriorating quality of life. Their treatments can generate massive medical costs as their health declines. In 1989, the gene responsible for CF, the CFTR gene, was cloned. The most common mutation found in the CFTR genes of the original CF patients studied is known as ??508, which accounts for… 10.3928/0090-4481-20030801-10